Neutrophil peptidyl arginine deiminase-4 has a pivotal role in ischemia/reperfusion-induced acute kidney injury

摘要: Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However, mechanisms underlying the sudden loss in function and tissue remain to be fully elucidated. Here, we investigated role peptidyl arginine deiminase-4 (PAD4), which converts citrulline plays epigenetic regulation inflammation, renal ischemia/reperfusion injury. PAD4 expression was highly induced infiltrating leukocytes 24 hours following ischemia reperfusion. This induction accompanied by citrullination histone H3 formation neutrophil extracellular traps kidneys wild-type mice. By contrast, PAD4-deficient mice did not form traps, expressed lower levels pro-inflammatory cytokines were partially protected from ischemia/reperfusion-induced AKI. Furthermore, recovered 48 hours after ischemia/reperfusion, whereas progressively worsened. Administration DNase I, degrades or PAD-specific inhibitor YW3-56 before ischemia, prevented Notably, transfer neutrophils wild-type, but mice, sufficient restore trap impair ischemia/reperfusion. Thus, pivotal